rs3773814

Positions:

• chr3-130996904-A-C
• chr3-130996904-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378687.1(ATP2C1):​c.2243+108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 813,968 control chromosomes in the GnomAD database, including 9,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1416 hom., cov: 33)
  • Exomes 𝑓: 0.15 (8218 hom.)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

Genes affected

ATP2C1 (HGNC:13211): (ATPase secretory pathway Ca2+ transporting 1) The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium ions. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-130996904-A-C is Benign according to our data. Variant chr3-130996904-A-C is described in ClinVar as [Benign]. Clinvar id is 1265320.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2C1	NM_001378687.1	c.2243+108A>C		intron_variant		ENST00000510168.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2C1	ENST00000510168.6	c.2243+108A>C		intron_variant		5	NM_001378687.1	P3

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18368 AN: 152080 Hom.: 1417 Cov.: 33

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.148 AC: 98167 AN: 661770 Hom.: 8218 AF XY: 0.146 AC XY: 52202 AN XY: 357402

Gnomad4 AFR exome AF: 0.0272

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.0803

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.121 AC: 18366 AN: 152198 Hom.: 1416 Cov.: 33 AF XY: 0.121 AC XY: 9017 AN XY: 74392

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0758

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.108

Alfa AF: 0.140 Hom.: 1626

Bravo AF: 0.110

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3773814; hg19: chr3-130715748;